BBOX1-IP3R3相互作用的计算感知揭示了三阴性乳腺癌中钙信号失调的抑制剂。

IF 2.3 3区 环境科学与生态学 Q3 CHEMISTRY, MULTIDISCIPLINARY
P Sangavi, G R Shri, S K Singh, K Langeswaran
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引用次数: 0

摘要

三阴性乳腺癌(TNBC)是最具侵袭性的乳腺癌类型,雌激素受体、孕激素受体和HER2表达阴性。信号通路的异常激活和特定类型的突变是TNBC进展的特征。肿瘤微环境中蛋白-蛋白相互作用在肿瘤侵袭性中起着至关重要的作用。破坏促进细胞进展、迁移和存活的信号通路,为靶向侵袭性TNBC开辟了一条有希望的途径。本研究强调BBOX1-IP3R3之间驱动侵袭性和顽固性TNBC的分子相互作用机制。BBOX1-IP3R3络合物的不稳定是通过虚拟筛选、分子动力学和基本动力学从各种数据库中获得的化合物来完成的。相互作用研究表明,这4个hit在界面处结合,具有较高的对接分数和最佳的结合自由能,具有较好的结合亲和力。此外,分子动力学模拟、PCA/FEL和MM/PBSA分析最终评估了化合物的结合势,并明确地稳定了复合物在高能状态下的特定构象或欺骗。因此,鉴定的化合物导致BBOX1-IP3R3相互作用的破坏,这有助于TNBC的治疗选择。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A computational perception of BBOX1-IP3R3 interaction uncovers inhibitors for dysregulated calcium signalling in triple negative breast cancer.

Triple Negative Breast Cancer (TNBC) is the most aggressive type of breast cancer unveiling negative expression on oestrogen receptors, progesterone receptors, and HER2. The anomalous activation of signalling pathways and specific types of mutations characterize the progression of TNBC. Protein-protein interaction in the tumour microenvironment plays a crucial role in tumour aggressiveness. Disrupting the signalling pathways that promote cell progression, migration, and survival opens up a promising avenue for targeting the aggressive form of TNBC. The present study emphasizes the molecular interaction mechanism driving the aggressive and recalcitrant TNBC between BBOX1-IP3R3. The BBOX1-IP3R3 complex destabilization was accomplished using compounds obtained from various databases through virtual screening, molecular, and essential dynamics. The interaction study revealed that the four hits bound at the interface and facilitated better binding affinity with the highest docking score and optimal binding free energy. In addition, the molecular dynamics simulation, PCA/FEL, and MM/PBSA analysis conclusively evaluate the binding potential of the compounds and unequivocally stabilize specific conformations or deception of the complexes in high-energy states. Thus, the identified compounds lead to the disruption of BBOX1-IP3R3 interaction, which aids in the therapeutic option of TNBC.

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来源期刊
CiteScore
5.20
自引率
20.00%
发文量
78
审稿时长
>24 weeks
期刊介绍: SAR and QSAR in Environmental Research is an international journal welcoming papers on the fundamental and practical aspects of the structure-activity and structure-property relationships in the fields of environmental science, agrochemistry, toxicology, pharmacology and applied chemistry. A unique aspect of the journal is the focus on emerging techniques for the building of SAR and QSAR models in these widely varying fields. The scope of the journal includes, but is not limited to, the topics of topological and physicochemical descriptors, mathematical, statistical and graphical methods for data analysis, computer methods and programs, original applications and comparative studies. In addition to primary scientific papers, the journal contains reviews of books and software and news of conferences. Special issues on topics of current and widespread interest to the SAR and QSAR community will be published from time to time.
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